IOV-4001 for Melanoma and Lung Cancer

Recruiting at 8 trial locations

Overseen By Iovance Biotherapeutics Study Team

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Iovance Biotherapeutics, Inc.

Must not be taking: Systemic steroids

Disqualifiers: Uveal melanoma, Untreated brain metastases, Organ transplant, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 1 year

53 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called IOV-4001 to determine its safety and effectiveness for individuals with difficult-to-treat skin or lung cancer. It targets those with melanoma that cannot be surgically removed or has spread, as well as advanced non-small-cell lung cancer (NSCLC). Participants should have melanoma that has worsened after specific treatments or NSCLC treated up to three times previously. Ideal candidates have a specific type of skin or lung cancer and have experienced progression after prior treatments. As a Phase 1 trial, this research aims to understand how the treatment works in people, offering participants the chance to be among the first to receive it.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude participants who require systemic steroid therapy at a dose of 10 mg/day prednisone or equivalent. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that IOV-4001 is likely to be safe for humans?

Research is investigating the safety of IOV-4001 for individuals with melanoma and lung cancer. These studies examine treatment tolerance and potential serious side effects.

For melanoma, early reports focus on safety data over a 28-day period, closely monitoring patient reactions shortly after treatment. While specific major side effects have not yet been identified, the trials are vigilant for any issues.

For lung cancer, similar research is underway. The same treatment, IOV-4001, is being studied in patients with advanced stages of the disease, with the primary goal of assessing safety.

Currently, data primarily comes from early studies, indicating that researchers are still learning about the treatment's safety. As trials progress, more information will become available. ^{1 2 3 4 5}

Why are researchers excited about this study treatment for melanoma and lung cancer?

Unlike the standard treatments for melanoma and lung cancer, which often rely on chemotherapy, immunotherapy, or targeted therapies, IOV-4001 is unique because it utilizes a novel approach involving genetically engineered cells. Researchers are excited about IOV-4001 because it is designed to enhance the body's immune response by modifying a patient's own T cells to better recognize and attack cancer cells. This treatment has the potential to provide a more personalized and targeted approach, potentially leading to more effective outcomes with fewer side effects compared to traditional therapies. By directly targeting cancer cells, IOV-4001 offers hope for improved management of these challenging cancers.

What evidence suggests that IOV-4001 might be an effective treatment for melanoma and lung cancer?

Research has shown that IOV-4001 might be a promising treatment for melanoma and lung cancer. This trial will include two separate cohorts: one for participants with unresectable or metastatic melanoma and another for those with Stage III or IV non-small-cell lung cancer. IOV-4001 uses specially modified immune cells, called tumor-infiltrating lymphocytes, to find and destroy cancer cells. Early studies suggest these cells can target cancer cells more effectively than some existing treatments. For melanoma, similar methods have shown potential, especially in patients who haven't responded to other treatments. In lung cancer, IOV-4001 is expected to strengthen the body's natural ability to fight tumors. These findings are hopeful and suggest that IOV-4001 could be a good option for these difficult-to-treat cancers. ^{1 2 4 6 7}

Who Is on the Research Team?

Iovance Biotherapeutics Study Team

Principal Investigator

Iovance Biotherapeutics

Are You a Good Fit for This Trial?

Adults with advanced melanoma or non-small-cell lung cancer (NSCLC) that can't be surgically removed. They must have had certain prior treatments, good organ function, and no untreated brain metastases or recent live vaccines. Participants need a measurable lesion for the study and agree to use effective birth control.

Inclusion Criteria

I have melanoma, worsened within 12 weeks after anti-PD-1/PD-L1 treatment, and received BRAF/MEK inhibitors if BRAF positive.

I have at least one tumor that can be surgically removed.

I have received specific treatments based on my group assignment.

Exclusion Criteria

I have not had a live vaccine within the last 28 days.

I have brain metastases that haven't been treated and are causing symptoms.

I have had another type of cancer in the last 3 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive an infusion of IOV-4001, a genetically modified autologous tumor-infiltrating lymphocytes (TIL) product

Up to 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

Up to 60 months

Open-label extension (optional)

Participants may opt into continuation of treatment long-term

Long-term

What Are the Treatments Tested in This Trial?

Interventions

• IOV-4001

Trial Overview The trial is testing IOV-4001 infusion's effectiveness and safety in treating unresectable/metastatic melanoma or advanced NSCLC. It will involve adults who meet specific health criteria and have received previous therapies relevant to their cancer stage.

How Is the Trial Designed?

Group I: Cohort 2 Experimental Treatment 1 Intervention

Participants with Stage III or IV non-small-cell lung cancer

Group II: Cohort 1 Experimental Treatment 1 Intervention

Participants with unresectable or metastatic melanoma

Who Is Running the Clinical Trial?

Iovance Biotherapeutics, Inc.

Lead Sponsor

Trials

26

Recruited

1,800+

Published Research Related to This Trial

PD-1/PD-L1 inhibitors are effective treatments for advanced non-small cell lung cancer (NSCLC), but currently, only a small number of patients can use them as first-line therapy due to strict selection criteria.

Combining PD-1/PD-L1 inhibitors with other treatments like chemotherapy, targeted therapy, or radiotherapy may enhance their effectiveness and allow more newly diagnosed NSCLC patients to benefit from immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[First-line Combination Immunotherapy in Advanced Non-small Cell Lung Cancer]. Peng, X., Zhou, Q.[2020]

In a study of 74 patients with metastatic non-small cell lung cancer (NSCLC) enrolled in early phase immunotherapy trials, those who had not previously received immunotherapy had a median overall survival (mOS) of 8.2 months, while those who had progressed on prior immunotherapy had a slightly better mOS of 10.5 months, indicating that prior treatment may not significantly hinder subsequent immunotherapy effectiveness.

Prognostic scores, particularly the Royal Marsden Hospital (RMH) score and the MD Anderson Cancer Center (MDACC) score, were effective in predicting overall survival, with a high ANC/ALC ratio (NLR) indicating poorer outcomes, suggesting that these scores can help identify patients who may not benefit from early phase immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predicting outcomes in patients with advanced non-small cell lung cancer enrolled in early phase immunotherapy trials. Maymani, H., Hess, K., Groisberg, R., et al.[2022]

In a study of 328 patients with KRAS+ non-small cell lung cancer (NSCLC), only 43 received immune checkpoint inhibitors (IO), showing that KRAS mutations do not significantly affect the efficacy of IO therapy.

The median progression-free survival (mPFS) and overall survival (OS) for KRAS+ patients treated with IO were similar to those of non-KRAS patients, suggesting that KRAS status should not be a determining factor in selecting patients for IO therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of Anti-PD1/PD-L1 Therapy (IO) in KRAS Mutant Non-small Cell Lung Cancer Patients: A Retrospective Analysis. Gianoncelli, L., Spitaleri, G., Passaro, A., et al.[2020]

In a study of 197 patients with metastatic non-small cell lung cancer (NSCLC) treated with immunotherapy, those with low baseline serum sodium levels (≤ 135 mEq/L) had significantly poorer clinical outcomes, including lower disease control rates and shorter overall survival (2.8 months vs. 11.6 months).

Low baseline serum sodium concentration was independently linked to worse disease control and overall survival, suggesting it could be a potential prognostic marker for patients undergoing immunotherapy for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low Baseline Serum Sodium Concentration Is Associated with Poor Clinical Outcomes in Metastatic Non-Small Cell Lung Cancer Patients Treated with Immunotherapy. Fucà, G., Galli, G., Poggi, M., et al.[2022]

In a study of 453 metastatic non-small cell lung cancer patients treated with immunotherapy, those who received radiotherapy (XRT) doses between 30 and 40 Gy showed significantly better overall survival compared to those who did not receive XRT.

Conversely, patients receiving low total doses of XRT (≤ 10 Gy) and certain fraction sizes (4.1-8 Gy) experienced worse outcomes, indicating that the specifics of radiotherapy can greatly influence the effectiveness of immunotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-World Analysis of the Impact of Radiotherapy on Immunotherapy Efficacy in Non-Small Cell Lung Cancer. Onn, A., Gottfried, T., Stemmer, A., et al.[2021]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05361174

NCT05361174 | A Study to Investigate the Efficacy and ... IOV-4001 is expected to have antitumor activity through its capacity to directly target and kill tumor cells in a manner that is similar to non-genome-edited ...

2. kucancercenter.org kucancercenter.org/cancer-clinical-trials/find-trial/clinical-trial-results/nct05361174

A Phase I/II, open-label study of PD-1 knockout tumor ... A Phase I/II, open-label study of PD-1 knockout tumor-infiltrating lymphocytes IOV-4001 in participants with unresectable or metastatic melanoma or Stage III or ...

3. clinicaltrials.cedars-sinai.edu clinicaltrials.cedars-sinai.edu/view/IOV-GM1-201

IOV-4001 in Melanoma or Non-Small-Cell Lung Cancer The purpose of this study is to determine whether an investigational drug called IOV-4001 is safe and beneficial in the treatment of patients with.

4. connect.careboxhealth.com connect.careboxhealth.com/en-US/trial/listing/342655

A Study to Investigate the Efficacy and Safety of an Infusion of ... This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non ...

5. crisprmedicinenews.com crisprmedicinenews.com/clinical-trial/solid-tumors-nct05361174/

Solid Tumors, (NCT05361174) - Clinical trial This study is the first-in-human study of IOV-4001, a genetically modified autologous tumour-infiltrating lymphocyte (TIL) product. IOV-4001 ...

6. iovance.com iovance.com/clinical-trials/

TIL and PBL Therapy Clinical Trials IOV-GM1-201 is Phase 1/2 study to evaluate the safety and efficacy of IOV-4001, a genetically modified autologous PD-1 knockout tumor-infiltrating lymphocytes ( ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-07362

A Study to Investigate the Efficacy and Safety of an Infusion ... This is a study to investigate the efficacy and safety of an infusion of IOV-4001 in adult participants with unresectable or metastatic melanoma or advanced non ...